BINDING OF SHC TO THE NPXY MOTIF IS MEDIATED BY ITS N-TERMINAL DOMAIN

She is an SH2-containing adapter protein that binds to and is phosphorylated by a large number of growth factor receptors, Phosphorylated She is able to interact with the GrbB-Sos complex which is responsible for mediating nucleotide exchange on Ras. We have shown previously that binding of She to the epidermal growth factor (EGF)-like receptor, c-ErbB-3, is through an NPXY motif (Prigent, S, A., and Gullick, W, J, (1994) EMBO J. 13, 2831-2841) shared by middle T antigen, TrkA, and EGF receptor, It has recently been reported that a region distinct from the SH2 domain is able to bind to tyrosine-phosphorylated proteins. In this paper we have used fusion proteins of various She domains to show that it is the N-terminal domain of She that is primarily responsible for binding EGF receptor and c-ErbB-3. Furthermore, by competition studies with synthetic phosphopeptides we have shown that this N-terminal domain binds to the previously identified NPXY motif.